This investigator-initiated protocol, in collaboration with Pangaea Pharmaceuticals, Inc., is a Phase I study with a primary objective to determine the toxicity of various doses of a DNA plasmid vaccine targeting the HPV-16 E7 antigen in HLA A2 positive individuals. The drug will be given as 6 intramuscular injections, one every three weeks to cohorts of three in a dose escalating fashion. Subjects must have anal or perianal high grade squamous intraepithelial lesion (HSIL), a preinvasive neoplasia with many similarities to cervical dysplasia. Secondary objectives will be to determine if there is evidence of a clinical or immune response. Although HSIL is common in the HIV population, this initial study will target an otherwise healthy, HIV negative population with HSIL to allow the collection of immunologic response data in subjects with intact immune systems. Anogenital examinations using high resolution anoscopy and tissue biopsies will be performed for disease assessment and correlative studies. Vaccine injections will be administered in the outpatient setting using the GCRC. Subsequent studies will likely evaluate this agent in HIV infected subjects.